The striking increase in reported genital herpes simplex virus (HSV) infection in the United States has increased concern and interest in the potentially devastating consequences of HSV infection in the neonate. Despite improved diagnosis of maternal disease and improved therapy of neonatal disease, morbidity and mortality remain high and the pathogenesis remains obscure. Immunologic evaluation of the newborn has revealed certain deficits that have possible relevance to HSV but these deficits fail to account for the severity of disease or for the sharp limitation of disseminated disease to the early weeks of life. This proposal derives from the hypothesis that humoral factors peculiar to the perinatal milieu contribute to HSV dissemination. Recent studies in this laboratory demonstrate that the occurrence of labor favorably influences survival of HSV in placental lymphocytes. It is proposed to examine this phenomenon in more detail and to test the hypothesis indirectly by performing the following series of experiments. 1. We will attempt to substantiate our preliminary observations that early intralymphocytic survival of HSV is primarily related to gestational age. 2. Placental lymphoid subpopulations will be studied comparatively for HSV permissiveness. 3. The effect of prostaglandins, arachidonic acid, oxytocin, and estrogens upon HSV survival will be evaluated. These substances all appear to be important in human parturition. 4. The effect of prostaglandin inhibitors upon HSV survival will be evaluated. 5. HSV-DNA and HSV-specific proteins will be examined to clarify the virus status, i.e. prolonged survival vs. replication. It is hoped that all of these studies will contribute to the understanding of the pathogenesis of neonatal HSV infection, particularly with respect to its propensity for dissemination and the narrow time period of vulnerability. The results may also help substantiate or negate evidence for a central role of prostaglandins in pathogenesis of HSV-related disease in general.